Achieving rapid and effective closure of surgical sites has attracted considerable attention throughout history. In more recent times, the proliferation of technological advances has resulted in the ability to access various parts of the human anatomy not previously contemplated. One example of this relates to the diagnostic and surgical use of the vasculature, and the attendant desire for prompt closure of such access sites. Examples of such percutaneous procedures include recanalization of atherosclerotic blood vessels, such as balloon angioplasty or artherectomy, cardiac mapping and treatment, placement of aortic balloon pumps, and other procedures. In recent years, both the types and numbers of such procedures utilizing percutaneous access to blood vessels have increased greatly.
These types of procedures generally involve the puncture of a blood vessel with a thin walled needle. A guidewire is then often placed through the needle into the blood vessel and the needle is withdrawn. An intravascular sheath is then advanced over the guidewire and into the lumen of the vessel. The sheath is then used as an ingress/egress means during the procedure, and is known generally as an introducer sheath. Following completion of the procedure, the introducer sheath may be removed, but this requires the application of prolonged manual pressure over the puncture site by a physician or other suitably trained medical personnel, as well as the use of other compression devices (e.g. sandbags) after manual compression is done. The time involved is extensive and costly. Also, patients are often treated with a variety of anticoagulant and thrombolytic agents, particularly in the setting of unstable angina or myocardial infarction. The discomfort and delay in mobilization and attendant morbidity, both physical and psychological, for patients is significant. This need for ongoing compression (usually 8-12 hours) frequently prolongs hospital stays and adds cost to the patient and society in general.
Alternatively, the sheath may be left in the puncture site for a prolonged period of time until the patient's coagulation status has returned to normal. Depending on the size of the vascular sheath, there may be an increased risk of bleeding to the patient, which may even require blood transfusion with its known attendant risks. In addition, there is a significant risk of injury to the blood vessel upon removal of the sheath, particularly if the sheath has been in place for a prolonged period of time. This includes the possible development of a pseudo-aneurysm or severe hematoma.
In view of the above, there is a need for a system and method that can effect hemostasis of a puncture site quickly, safely, and within patient comfort ranges. Such system and method ideally would effect this closure without the need for manual compression, other compression devices, or suturing at the surgical site.
It is known to place procoagulants, tissue adhesives, or similar materials at puncture sites or other surgical locations to facilitate hemostasis. See, for example, Pfab, et al., "Local Hemostasis of Nephrostomy Tract with Fibrin Adhesive Sealing in Percutaneous Nephrolithotomy," European Urology, vol. 13, pp. 1 18-21, 1987 (fibrin); Abbott, et al., "Microcrystalline Collagen as a Topical Hemostatic Agent for Vascular Surgery," Surgery, vol. 75, no. 6, pp. 926-33, Jun. 1974 (collagen); and Lunderquist, et al., "Transhepatic Catheterization and Obliteration of the Coronary Vein in Patients with Portal Hypertension and Esophageal Varices," The New England Journal of Medicine, vol. 291, no. 13, pp. 646-49, Sep. 26, 1974 (thrombin). Numerous other references describe use of such hemostatic agents for various purposes, in various combinations, and with certain other materials. For example, it is quite well known to use a collagen based fleece plug or tampon to seal a percutaneous access site. See, e.g., Krause, et al., "Utility of a Percutaneous Collagen Hemostasis Device: To Plug or Not to Plug?," Journal of the American College of Cardiology, vol. 25, no. 7, pp. 1685-92. June 1995.
Other combinations of materials are known for use in wound closure, such as in U.S. Pat. No. 4,453,939 titled "Composition for Sealing and Healing wounds" in winch a collagen carrier is coated with a mixture of a fibrinogen component, and thrombin component, and optional additional additives to promote the infiltration and growth of fibroblasts. Sheets or coatings are similarly well known for closing wounds by promoting coagulation of blood using thrombin, collagen, fibrin and related products, as described in U.S. Pat. No. 4,683,142. In many references, the components are in powdered or lyophilized form, for example as in U.S. Pat. No. 4,515,637 titled "Collagen-Thrombin Compositions." In this patent, the collagen product is readily absorbable when placed in vivo, and is storage stable. This latter issue of thrombin stability has generally been problematic, and has led to select oil of lyophilized rather than reconstituted thrombin to achieve long term stability.
The embodiments of either powdered, lyophilized, paste, tampon or solid type of hemostatic agents are inadequate for achieving certain advantages in closure of access sites in a patient's vasculature. Indeed, even a liquid or aqueous composition useful for promoting hemostasis in certain applications might be inadequate for such specialized purposes as discussed below. One such example is found in U.S. Pat. No. 5,290,552, titled "Surgical Adhesive Material," in which is described a surgical adhesive in an aqueous composition having fibrinogen, FXIII, collagen, thrombin, Ca.sup.2, and an optional antifibrinolytic agent. The material is formed from the patient's plasma thus avoiding the difficult challenges of determining proper reagents for concentration or isolation of the fibrinogen. Avoidance of solid forms of hemostatic materials is also an advantage to certain compositions, such as those in an aqueous, gel, or paste form. Such structural forms allow for packing or molding of the hemostatic material to achieve better conformity with the cavity or wound to be healed.
In U.S. Pat. No. 4,891,359, titled "Hemostatic Collagen Paste Composition," a paste or dough mixture comprises 5 to 30% of a water insoluble crosslinked collagen powder of 10 to 100 mesh particle size and 70 to 95%, of water or an aqueous saline solution. In one embodiment, an aqueous glycerine solution containing a hemostatic enhancing amount of thrombin is added, with the resulting paste having a consistency suitable for packing into a squeeze tube or syringe package. Various additives may be employed to enhance pH compatibility and to prolong the stable life of the thrombin in the paste composition.
Other references arc known which address ways to prepare gels as drug delivery vehicles onto the skin or into a body cavity of a mammal, such as in U.S. Pat. Nos. 5,437,292, 5,298,260 and 5,292,516. In U.S. Pat. No. 5,437,292 a gel which contains fibrinogen and thrombin is designed to be packed around a blood vessel or organ, with a compression of the gel proximally provided to prompt closure of a puncture site. In U.S. Pat. No. 5,298,260, a thermoreversible drug carrying gel is formed for topical use on, for example, a burned portion of a patient's skin. In one embodiment, the gel would have characteristics of a pH about 7 and an osmolality of about 650 mOsm/kg in the liquid state, and then upon thermal transition to a gel the material would be at a pH of about 7 and an osmolality of about 290 mOsm/kg. While the reference contains no suggestion of using the gel material for a non-thermal reversible hemostasis application, there is disclosure of certain desirable attributes of the final product form.
Similarly, in U.S. Pat. No. 4,592,864, an aqueous atelocollagen solution is disclosed. This solution is designed for injection into living bodies as a means of regenerating collagen fiber, and is a syringe injectable fluid under the pH and osmolality conditions close to those in living bodies, and which forms collagen fiber when equilibrated with biological conditions after injection. This product is designed to be injected into ruptured tissues to fill the area of the rupture without incision. A sodium phosphate buffer is used to control the pH and osmolality of the solution so that at room temperature the solution remains as a liquid and once injected into a living organism the solution quickly regenerates collagen fiber.
Although many uses of the above hemostatic materials are disclosed, and many types of such materials are used in connection with closure of vascular access sites, no combination exists which provides an injectable liquid solution procoagulant as described below, for the specific uses as described below, and which achieves the advantages discussed.